Hemozoin is a hydrophobic hem polymer which is the detoxification product of the hem molecules found in the food vacuole of Plasmodium protozoa, and it can be produced by digestion of host hemoglobin by Plasmodium protozoa. Like CpG DNA, hemozoin acts as a ligand of Toll-like receptor 9 (TR9). It is reported that the Toll-like receptor 9 is involved in the innate immune response to various pathogens including Plasmodium. In other words, immune system is activated in a MyD88-dependent manner when Toll-like receptor 9 recognizes a ligand.
The hemozoin synthesized from hemin chloride is called β-hematin (see non-patent document 1).
It is reported that hemozoin activates in vitro spleen cells and dendritic cells of mice (see patent document 1). It is also reported that hemozoin has an adjuvant effect on the antibody production of ribonuclease A in mice (see patent document 2).
In addition, it is reported that β-hematin has an effect as an adjuvant of DNA vaccines (see non-patent document 2), and (see non-patent document 2), and it is further reported that β-hematin functions as a ligand other than TLR9 DNA molecules (non-methylated DNA chain that is called a so-called CpG motif) (see non-patent document 3).
However, there was no disclosure that hemozoin and β-hematin could be used as a vaccine adjuvant for potentiating in vivo effect of allergen vaccines or bacterial or viral infection vaccines.
Patent document 1: International patent publication No. WO 2006/061965 pamphlet
Patent document 2: U.S. Pat. No. 5,849,307
Non-patent document 1: Slater et al., Proc. Natl. Acad. Sci. U.S.A. 88: 325-329, 1991
Non-patent document 2: Infect. Immun. 2002 July; 70(7):3939-43
Non-patent document 3: J Exp Med. 2005 Jan. 3; 201(1):19-25